The coolest and strangest thing in medicine is What? Some people think it is the placebo effect. Although we cannot predict the future or move objects with our thoughts, the placebo effect is almost as magical as these two.
“Placebo effect” refers to the fact that only “believing it to be effective” for an ineffective therapy or intervention can improve health and change cognition-which seems to prove irrefutably that spirit has almost magical power and can surpass matter.
Of course, this is not real magic. Our belief is What? It is the subjective response of the physical process in the brain. It is neurochemical events and current events in the brain and their downstream effects that produce the placebo effect.
In some cases, the placebo effect can also be seen as a conditioned reflex: although there is no initial stimulus, the learned psychological reaction will still occur.
For scientists, the placebo effect is not only an amazing phenomenon, but also causes trouble in research methods.
Researchers must try their best to eliminate the influence of the subjects’ expectations so as to determine which of the observed effects in inside are really the result of the intervention.
In honor of the mysterious and maddening placebo effect, and in order to promote the study of this most fascinating manifestation of human psychology, we summarize the following 10 surprising findings related to placebo.
Even if you know it is a placebo, it is equally effective
It is generally believed that deception is essential to induce the placebo effect, and doctors should induce patients to think that an ineffective therapy is a powerful drug or has a similar effect.
Because of this cheating factor, mainstream medicine has long regarded deliberately inducing placebo effect as immoral behavior.
However, nearly 10 years ago, researchers pointed out that the symptoms of patients with irritable bowel syndrome are still improved compared with those without any treatment after taking the “open placebo” which is known to be ineffective.
This must be because although they know that the therapy is not effective for the body, they still have faith and expectation for its effect (or perhaps it is a conditioned reflex to placebo and does not need the patient’s positive faith).
Since then, other studies have shown that open placebos have effects on many diseases including backache  and hay fever .
Some experts said that the publication of placebos “at least partially bypassed the ethical barriers to the clinical use of placebos.” However, some experts said that there is still a lack of sound research in this field.
It should also be pointed out that some studies have not yielded positive results, such as the public placebo did not accelerate wound healing .
Brand, color and medical related items can all enhance the placebo effect
In addition to disclosing placebos, there is evidence that the efficacy of placebos is related to their forms of deception. The stronger the effect we imagine, the greater the profit.
This means that four placebo tablets are better than two, and placebo injections (which have nothing but saline) are stronger than placebo tablets. Even some studies have found that when treating osteoarthritis, a placebo injection is more effective than taking real medicine .
In addition, depending on the treatment of diseases, tablets with certain colors and instructions are especially effective. For example, blue placebo tablets are more sedative than pink ones , and branded placebos are more effective than those without labels .
Some people are more likely to have a placebo effect than others
People with certain personality traits are more likely to have placebo effect. This is well understood, because the placebo effect depends on our beliefs and expectations, and some people may identify with these beliefs and expectations more easily and enthusiastically than others.
The findings include: optimists are more likely to respond to placebo for pain relief . Those who scored higher on tenacity and friendliness also responded better to the analgesic placebo , which may be related to the interaction between doctors and patients when inducing the placebo effect.
Strangely, the characteristics related to the placebo response vary with the disease being treated-for example, in stress therapy, a study found that instead, subjects with pessimistic personalities and poor empathy had better responses to the placebo .
Current evidence also shows that personality traits appear to have an important effect on placebo response, while age and gender have little effect.
Some doctors are better at inducing placebo effect than others
The placebo effect depends on whether the patient believes that the treatment he receives is effective. However, some doctors are better at strengthening their hopes and expectations for treatment than others.
This is also confirmed by research: a study on the treatment of allergic reactions with placebo injection points out that if a doctor with a mild and credible attitude is responsible for the injection, the symptoms of the patient will be improved more .
It may also be helpful for patients to feel that they are “the same kind of people” as doctors: another study found that when a patient believes that the attending doctor and he have the same values and personal beliefs, his subjective pain after clinical operation will be reduced .
Placebo can also improve creativity and cognitive performance
We usually think that the effect of placebo is medical intervention, especially pain relief. However, there is growing evidence that placebos have other effects, including improving our physical and mental performance.
As far as athletic ability is concerned, many studies have found placebo effect in speed, strength and endurance. In a placebo-like study, the researchers asked cyclists to train until they were exhausted. The results showed that if their clocks were secretly modified to move slower, the cyclists’ persistence time would be significantly prolonged .
In terms of creativity, in one study, the experimental group outperformed the control group in the creativity test after smelling a smell that is said to improve creativity. The control group also smelled the same smell, but no one told them that the smell has special benefits .
In another experiment, the subjects received placebo non-invasive brain stimulation and completed a learning task. The placebo group thought that their brains were slightly stimulated by electric current, but they did not. They thought that this kind of stimulation could improve their mental function. Results In the following learning tasks, the placebo group was more accurate than the control group, and the reaction time was shortened faster .
The researcher said: “Our conclusion is that the expectation induced in the experiment can affect the cognitive function of healthy adult subjects.”
There is even “placebo sleep.”
The manifestation of placebo effect is almost endless.
For example, there is a strange case where researchers deceive subjects into believing that they sleep longer than they actually do, and then observe how this affects their performance the next day.
The deception of the researchers is to let the subjects take various psychological measurements and then give some of them wrong feedback on the deep sleep time (REM REM sleep time).
After hearing that they had got enough sleep, these subjects performed better in language and arithmetic tests .
There are other imaginative examples and manifestations of the placebo effect. For example, a study found that when hotel cleaners learned that their work could be counted as physical exercise, their health conditions really improved, including body weight, body mass index, body fat, waist-hip ratio and blood pressure .
Another interesting study may also be explained by the placebo effect: people who believe they exercise more than their peers tend to live longer than their peers, no matter how much they actually exercise .
Animals Can Realize Placebo Effect
Effective therapies are often compared with placebo in drug trials using animals, which is similar to the process of human drug trials.
In comparison, researchers often find that a considerable number of animals in the placebo group also have therapeutic reactions, such as an anti-epileptic drug test for dogs and a dietary intervention test for horse muscle stiffness.
However, there is a loophole in the interpretation of these results: these placebo effects may exist in the owners of animals, who may treat animals in different ways when they believe that their animals are really receiving medical treatment or nutrition supplement.
However, several laboratory studies on rodents have proved that animals do show some placebo effect.
Researchers have matched an effective drug (such as morphine) with a specific taste or smell, and then they have proved that even if the drug is removed and only the taste or smell is reproduced, it can also have analgesic effect on rodents .
In this example, the source of the placebo effect is conditioned reflex rather than animal expectation, but this may also be part of the principle of the human placebo effect.
As Edward Ernst, a medical expert specializing in non-mainstream therapies, said: “Most of the placebo effect we think has been found in animals.”
Just because you believe a certain therapy is beneficial, it will produce a placebo effect.
It can be deduced that if you have negative expectations, your symptoms will worsen. Researchers did find this phenomenon and called it “nocebo effect”.
The twin brother of placebo effect should not be underestimated.
A meta-analysis of an analgesic study (in which some subjects were told that an ineffective ointment or tablet would increase pain sensation in some people) showed that the scale of nocebo effect was roughly equivalent to the placebo effect .
Interestingly, even if patients were given real painkillers instead of fake treatments, nocebo effect would still appear.
One study told subjects that their pain would increase after the analgesic treatment was stopped. Normally, even if the drug is stopped, the psychological effect of the analgesic will continue for a while, but for these subjects, its effect suddenly disappeared, as if the negative expectation of the subjects dispelled the real effect of the analgesic .
The practical significance of these findings is obvious, at least, you need to pay attention to them when you read the explanation of the side effects of new drugs.
For many psychological researchers, the placebo effect is a problem
Although the placebo effect is very interesting, it can be maddening to researchers who intend to prove the efficacy of psychological intervention.
Psychological expectation strongly and universally affects our thinking, emotion and behavior, making many researches have to be carefully designed, otherwise it is difficult to interpret the results.
In a 2013 paper entitled “The Common Placebo Problem in Psychology” , Walter Boot’s team at Florida State University pointed out that in fact, many psychological studies failed to make subjects in different experimental groups have the same expectations.
They explained that it is not enough to set up a positive control group alone, because the subjects in the control group are not necessarily like the intervention group and expect the experiment to produce beneficial or powerful effects.
Bout and his colleagues pointed out that the way to solve this problem is to measure the expectations of the subjects and take measures to make the expectations of the control group and the intervention group as equal as possible. They concluded: “We hope that future research can have better design and can better contain the placebo effect and provide more credible evidence for the efficacy of intervention.”
The placebo effect seems to be increasing
Strangely, the placebo effect seems to be on the increase in recent years, which is shown in antipsychotics , antidepressants  and analgesics .
Among them, the placebo effect of analgesics only became stronger in the United States. Jeffrey Mogil, the research leader, told Nature News: “We were shocked to find this effect.”
Specifically, in the 1990s, they found that the proportion of subjects taking effective drugs reporting pain relief was 27% higher than those taking placebo, but by 2013, the gap had narrowed to 9%.
One explanation is that new drug trials have become larger and more sophisticated, especially in the United States, so subjects taking placebos have also experienced more drama and tension.
Another possibility is that the public has a better understanding of the placebo effect and also knows that it can really affect symptoms (such as reducing brain activity related to pain), not just illusions.
Last year’s pain journal, anesthesiologist Gary Bennett put forward this view .
He even argued that since the word “placebo” could cause such a strong placebo effect, it should not be used in drug trials, and the word “placebo” should be avoided in the instructions and instructions to patients.
In any case, the placebo effect will continue to exist, no matter how hard we try to control, hide and understand it. For a long time to come, inside will certainly continue to confuse and surprise us.
- Kaptchuk, T. J., Friedlander, E., Kelley, J. M., Sanchez, M. N., Kokkotou, E., Singer, J. P., … Lembo, A. J. (2010). Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome. PLoS ONE, 5(12), e15591. https://doi.org/10.1371/journal.pone.0015591
- Carvalho, C., Caetano, J. M., Cunha, L., Rebouta, P., Kaptchuk, T. J., & Kirsch, I. (2016). Open-label placebo treatment in chronic low back pain. PAIN, 157(12), 2766–2772. https://doi.org/10.1097/j.pain.0000000000000700
- Schaefer, M., Sahin, T., & Berstecher, B. (2018). Why do open-label placebos work? A randomized controlled trial of an open-label placebo induction with and without extended information about the placebo effect in allergic rhinitis. PLOS ONE, 13(3), e0192758. https://doi.org/10.1371/journal.pone.0192758
- Mathur, A., Jarrett, P., Broadbent, E., & Petrie, K. J. (2018). Open-label Placebos for Wound Healing: A Randomized Controlled Trial. Annals of Behavioral Medicine, 52(10), 902–908. https://doi.org/10.1093/abm/kax057
- Bannuru, R. R., McAlindon, T. E., Sullivan, M. C., Wong, J. B., Kent, D. M., & Schmid, C. H. (2015). Effectiveness and Implications of Alternative Placebo Treatments. Annals of Internal Medicine, 163(5), 365. https://doi.org/10.7326/m15-0623
- Blackwell, B., Bloomfield, S., & Buncher, C. R. (1972). DEMONSTRATION TO MEDICAL STUDENTS OF PLACEBO RESPONSES AND NON-DRUG FACTORS. The Lancet, 299(7763), 1279–1282. https://doi.org/10.1016/s0140-6736(72)90996-8
- Faasse, K., Martin, L., Grey, A., Gamble, G., & Petrie, K. (2015). Impact of Brand or Generic Labeling on Medication Effectiveness and Side Effects. Health Psychology DOI: 10.1037/hea0000282
- McRae, C., Cherin, E., Yamazaki, T. G., Diem, G., Vo, A. H., Russell, D., … Freed, C. R. (2004). Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial. Archives of General Psychiatry, 61(4), 412–20. https://doi.org/10.1001/archpsyc.61.4.412
- Geers, A. L., Wellman, J. A., Fowler, S. L., Helfer, S. G., & France, C. R. (2010). Dispositional optimism predicts placebo analgesia. The Journal of Pain : Official Journal of the American Pain Society, 11(11), 1165–71. https://doi.org/10.1016/j.jpain.2010.02.014
- Peciña, M., Azhar, H., Love, T., Lu, T., Fredrickson, B., Stohler, C., and Zubieta, J. (2012). Personality Trait Predictors of Placebo Analgesia and Neurobiological Correlates Neuropsychopharmacology DOI: 10.1038/npp.2012.227
- Darragh, M., Booth, R. J., & Consedine, N. S. (2014). Investigating the ‘placebo personality’ outside the pain paradigm. Journal of Psychosomatic Research, 76(5), 414–421. https://doi.org/10.1016/j.jpsychores.2014.02.011
- Howe, L. C., Goyer, J. P., & Crum, A. J. (2017). Harnessing the placebo effect: Exploring the influence of physician characteristics on placebo response. Health Psychology, 36(11), 1074-1082.http://dx.doi.org/10.1037/hea0000499
- Losin, E. A. R., Anderson, S. R., & Wager, T. D. (2017). Feelings of Clinician-Patient Similarity and Trust Influence Pain: Evidence From Simulated Clinical Interactions. The Journal of Pain, 18(7), 787–799. https://doi.org/10.1016/j.jpain.2017.02.428
- Morton, R. H. (2009). Deception by manipulating the clock calibration influences cycle ergometer endurance time in males. Journal of Science and Medicine in Sport, 12(2), 332–337. https://doi.org/10.1016/j.jsams.2007.11.006
- Rozenkrantz, L., Mayo, A. E., Ilan, T., Hart, Y., Noy, L., & Alon, U. (2017). Placebo can enhance creativity. PLOS ONE, 12(9), e0182466. https://doi.org/10.1371/journal.pone.0182466
- Turi, Z., Bjørkedal, E., Gunkel, L., Antal, A., Paulus, W., & Mittner, M. (2018). Evidence for Cognitive Placebo and Nocebo Effects in Healthy Individuals. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-35124-w
- Draganich C, and Erdal K (2014). Placebo Sleep Affects Cognitive Functioning. Journal of experimental psychology. Learning, memory, and cognition PMID: 24417326
- Crum, A.J. & Langer, E.J. (2007). Mind-set matters. Exercise and the placebo effect. Psychological Science, 18, 165-171.
- Zahrt, O. H., & Crum, A. J. (2017). Perceived physical activity and mortality: Evidence from three nationally representative U.S. samples. Health Psychology, 36(11), 1017-1025. http://dx.doi.org/10.1037/hea0000531
- Keller, A., Akintola, T., & Colloca, L. (2018). Placebo Analgesia in Rodents: Current and Future Research. International Review of Neurobiology, 1–15. https://doi.org/10.1016/bs.irn.2018.02.001
- Petersen, G. L., Finnerup, N. B., Colloca, L., Amanzio, M., Price, D. D., Jensen, T. S., & Vase, L. (2014). The magnitude of nocebo effects in pain: a meta-analysis. PAIN, 155(8), 1426-1434.
- Bingel, U., Wanigasekera, V., Wiech, K., Ni Mhuircheartaigh, R., Lee, M. C., Ploner, M., & Tracey, I. (2011). The effect of treatment expectation on drug efficacy: imaging the analgesic benefit of the opioid remifentanil. Science Translational Medicine, 3(70), 70ra14. https://doi.org/10.1126/scitranslmed.3001244
- Boot, W. R., Simons, D. J., Stothart, C., & Stutts, C. (2013). The pervasive problem with placebos in psychology: Why active control groups are not sufficient to rule out placebo effects. Perspectives on Psychological Science, 8(4), 445-454.
- Leucht, S., Arbter, D., Engel, R. R., Kissling, W., & Davis, J. M. (2008). How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials. Molecular Psychiatry, 14(4), 429–447. https://doi.org/10.1038/sj.mp.4002136
- Dunlop, B. W., Thase, M. E., Wun, C.-C., Fayyad, R., Guico-Pabia, C. J., Musgnung, J., & Ninan, P. T. (2012). A meta-analysis of factors impacting detection of antidepressant efficacy in clinical trials: the importance of academic sites. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 37(13), 2830–6. https://doi.org/10.1038/npp.2012.153
- Tuttle, A. H., Tohyama, S., Ramsay, T., Kimmelman, J., Schweinhardt, P., Bennett, G. J., & Mogil, J. S. (2015). Increasing placebo responses over time in U.S. clinical trials of neuropathic pain. Pain, 156(12), 2616–26. https://doi.org/10.1097/j.pain.0000000000000333
- Bennett, G. J. (2018). Does the word “placebo” evoke a placebo response? PAIN, 159(10), 1928–1931. https://doi.org/10.1097/j.pain.0000000000001269